Age is an independent risk factor for NIDDM. A decline in insulin secretion and a decrease in insulin action occur as people age. This combination makes people more prone to develop NIDDM. A similar phenomenon occurs in Wistar rats. We are using the beta cells from Wistar rats in the aged colony at the GRC to study changes with insulin secretion. We found that mRNA for insulin is preferentially diminished in islets, with glucokinase and glucagon messages unaffected. Therefore, one can envision when a stress is put on the system so more insulin is required, diabetes could result. We are exploring what factors lead to this diminution of insulin message and the possibility that we can prevent or reverse it. We have found the GLP-1 can somewhat restore the number of cells that are again responsive.